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New Jounce CEO Murray Aims to Place the Right Immuno-Oncology Bets

Jounce Therapeutics’ founding idea—to simultaneously tackle several different immune-system-based approaches for treating cancer—could be both a blessing and a curse. On one hand, the Cambridge, MA-based startup could unearth a number of programs Big Pharma could find attractive enough to partner, and bring in some big dollars. On the other, Jounce could spread itself too thin.

Indeed, avoiding that fate is one of the big challenges ahead for Murray, the former Merck executive who will officially start in his new gig as Jounce’s head man this coming Monday. Murray is taking charge of an ambitious bet by Third Rock Ventures, which committed $47 million to start Jounce early last year. The plan: to pool together the work of a group of cancer immunotherapy experts across the country, and come up with drugs that harness the power of the immune system to fight cancer in a variety of different ways, rather than homing in on one single approach.

The road ahead will be tough. Cancer immunotherapy has quickly become one of the hottest, and most competitive, fields in life sciences. Big Pharmas and small companies across the globe are all racing to find the best combination of treatments, wheeling and dealing in a variety of ways. A “gold rush,” Murray says, is underway, as a new wave of so-called PD-1 inhibitors, which remove a cloaking device that tumors use to hide from the immune system, are speeding towards the market. With all those forces raging, how does Jounce plan to differentiate itself and compete?

Murray points to two things in particular, each of which fueled his decision to come to Jounce. One is insight and feedback from Jounce’s set of founders—James Allision and Pam Sharma of MD Anderson; Thomas Gajewski of the University of Chicago; Drew Pardoll of Johns Hopkins University School of Medicine; and Georgetown University Medical Center’s Louis Weiner. The other, Murray says, is early investments Jounce made in drug technologies that might either work synergistically with PD-1 inhibitors, or which might help treat cancer types for which PD-1 inhibitors aren’t as effective. That’s particularly important given how crowded the field has become.

“I was very, very impressed with the foresight of that, [it] is going to help us really pinpoint where to go with a new mechanism,” he says. “That doesn’t mean other people can’t do that or it’s not going to be very competitive, but I think [it’s] a better approach.”

Jounce has said that its drug prospects would come from three major categories. One of those is checkpoint inhibitors, which shut off molecular switches that otherwise cloak cancer from the immune system. (PD-1 inhibitors are one type of checkpoint inhibitor.) Another is co-stimulatory molecules, which boost the immune system’s response to cancer cells. The third category is drugs that hit molecular targets in the tumor microenvironment that otherwise make the cancer cells less vulnerable to the immune system.

That’s a lot of potential approaches to choose from, and for a small company like Jounce, it’s critical not to pour too many resources into something exceedingly risky early on. So while Murray declined to disclose which specific molecular targets Jounce plans to go after first, he did say that the company has something of a “two step” plan. First, Jounce will develop checkpoint inhibitors, a safer scientific bet. Not PD-1 blockers, of course—Jounce, Murray says, is very cognizant of the big commercial impact those molecules are about to have.

The plan is to advance several of these prospects in the hopes of filing at least one investigational new drug application with the FDA in early 2016 to begin clinical trials, Murray says.

Next, Jounce will move on to riskier science: drugs that would modify the tumor microenvironment. The idea, Murray says, is to find out why certain tumors aren’t open to the immune system, and force a change.

Those discussions, however, are far away. For now, Jounce only has certain unspecified “bona fide lead programs” that are being fine-tuned and are close to the point of formal preclinical development. Meaning the critical early decisions are coming for Murray.

“We’re going to need to take a hard look at where to place the bets,” he says. “The key is to be crisp about the molecules that we think scientifically will be the winners.”